Tau proteins are a type of microtubule-associated protein. Tau proteins are particularly abundant in neurons of the central nervous system and have a function of binding to a protein called tubulin which mainly constitutes a cytoskeleton component, microtubules, and thereby stabilizing microtubules and promoting tubulin assembly into microtubules. In addition to tubulin, Tau proteins are also known to associate with other signaling molecules (Src family, PI3K, Fyn) and to promote neurite outgrowth and elongation of nerve growth cones (see, for example, Non-patent Documents 1 to 3).
Phosphorylation of Tau proteins can occur excessively in vivo. When Tau proteins are excessively phosphorylated, their binding with tubulin is inhibited, as a result of which microtubules are reduced or microtubules are destabilized and the intracellular substance transport is suppressed (see, for example, Non-patent Documents 4 and 5). Excessively phosphorylated Tau proteins aggregate with each other to form aggregates called neurofibrillary tangles. Alzheimer's disease and progressive supranuclear palsy that involve such formation of neurofibrillary tangles are classified into neurodegenerative diseases called tauopathy.
There have been proposed methods of treating a tauopathy by compensating the functions of Tau proteins. For example, U.S. Pat. No. 5,580,898 suggests the use of paclitaxel [TAXOL (registered trademark)] for the treatment of Alzheimer's disease patients through stabilization of microtubules. Further, Patent Document 1 describes an effective therapeutic method of tauopathy using a microtubule stabilizer, epothilone D.
Meanwhile, mainly in the Oriental countries, earthworm extracts and dry earthworm powders have been used since ancient times as preventive agents and therapeutic agents for various diseases, and examples of their use that have been known include bladder stone-reducing agents, bladder stone excretion-promoting agents, therapeutic agents for jaundice, oxytocics, tonic agents, hair growth agents, aphrodisiacs, antipyretics, therapeutic agents for convulsion, blood circulation promoters, therapeutic agents for hemiplegia, indirect analgesics, diuretics, antiasthmatics and antihypertensive agents.
However, no report has been made on the use of earthworms for the prevention and treatment of tauopathy such as Alzheimer's disease.